The Journal of Prevention of Alzheimer's Disease最新文献

{"title":"Reevaluating the sleep-dementia link: Methodological gaps and future directions.","authors":"Julián Benito-León, Carla María Benito-Rodríguez","doi":"10.1016/j.tjpad.2025.100085","DOIUrl":"10.1016/j.tjpad.2025.100085","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100085"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial dysfunction as the missing link between circadian syndrome and dementia.","authors":"Yu-Hsiang Lin, Kuo-Jen Lin, Po-Ting Lin","doi":"10.1016/j.tjpad.2025.100125","DOIUrl":"10.1016/j.tjpad.2025.100125","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100125"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of APOE ε4 on performance of CSF biomarkers in differentiating clinical Alzheimer's disease.","authors":"Yan Wang, Fangyu Li, Qi Qin, Tingting Li, Qi Wang, Yan Li, Ying Li, Jianping Jia","doi":"10.1016/j.tjpad.2025.100065","DOIUrl":"10.1016/j.tjpad.2025.100065","url":null,"abstract":"<p><strong>Introduction: </strong>Apolipoprotein E ε4 (APOE ε4) bring the higher risk of Alzheimer' Disease (AD). It is essential to evaluate whether the diagnostic performances and critical values of cerebrospinal fluid (CSF) biomarkers are influenced by APOE ε4, which has guiding significance for the clinical practical application.</p><p><strong>Methods: </strong>The differences in CSF biomarkers and their performances between APOE ε4 carriers and non-carriers in distinguishing AD, mild cognitive impairment (MCI) and preclinical AD from normal controls (NCs) were analyzed. The receiver operating characteristic (ROC) curves were generated to compare the area under the curve (AUC) between APOE ε4 carriers and non-carriers, as well as the critical values corresponding Youden Index.</p><p><strong>Results: </strong>In a cross sectional convenience sample of 1610 participants, lower Aβ42 and Aβ42/Aβ40 and higher p-Tau 181/Aβ42 in CSF were observed among APOE ε4 carriers than non-carriers in NC, MCI, and AD groups (P< 0.05). The performance of CSF p-tau/Aβ42 in distinguishing MCI from NC among APOE ε4 carriers was superior to non-carriers [AUC: 0.714 (95%CI: 0.673- 0.752) vs 0.600 (95%CI: 0.564- 0.634), P< 0.001], although it was similar in distinguishing AD from NC between APOE ε4 carriers and non-carriers [AUC: 0.874 (95%CI: 0.835-0.906) vs 0.876 (95%CI: 0.843- 0.904)]. In the longitudinal cohort of 254 participants, the association of CSF Aβ42, Aβ42/Aβ40 and p-Tau181/Aβ42 with cognitive decline were stronger in APOE ε4 carriers compared to non-carriers (P< 0.05). Meanwhile, the critical values were different depending on APOE genotype.</p><p><strong>Discussion: </strong>The CSF level of p-Tau181/Aβ42 was significantly different between APOE ε4 carriers and non-carriers at different stages of AD. The results indicate that the performances of CSF biomarkers are influenced by APOE ε4, which should be considered in the practical application.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100065"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the causal role of lipid metabolites in Alzheimer's disease: A mendelian randomization study.","authors":"Haoxiang Hu, Jiesheng Mao, Yunhan Zhao, Yihan Zhang, Caixiang Zhuang, Jiang Hai He, Xiaokai Yang","doi":"10.1016/j.tjpad.2025.100067","DOIUrl":"10.1016/j.tjpad.2025.100067","url":null,"abstract":"<p><strong>Background: </strong>The causal relationship between lipid metabolites and Alzheimer's disease (AD) remains unclear and contradictory. This study aimed to systematically assess the causal relationship between lipid metabolites and AD.</p><p><strong>Methods: </strong>A two-step bidirectional Mendelian Randomization (MR) study was employed. The principal analytical technique used to evaluate causation was inverse variance weighting (IVW). Furthermore, mediation analysis was conducted to evaluate the possible function of lipidomes as mediators in the lipid-AD pathway.</p><p><strong>Results: </strong>Among the 213 lipid metabolites analyzed, significant causal associations with AD were identified Cholesterol esters in large LDL(L-LDL-CE) (OR = 1.236, 95 %CI = 1.052-1.453, P = 0.010), Total cholesterol in large LDL(L-LDL-TC) (OR = 1.506, 95 %CI = 1.235-1.835, P < 0.001), Total cholesterol in medium LDL(M-LDL-TC) (OR = 1.378, 95 %CI = 1.132-1.677, P = 0.001). Mediation analysis further revealed ceramide (d42:2) and phosphatidylinositol (PI) (18:1_18:1) as potential mediators in this relationship.</p><p><strong>Conclusion: </strong>The identification of specific lipid metabolites with causal effects on AD provides new insights into AD pathogenesis and highlights potential targets for preventive strategies.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100067"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of dietary diversity, genetic susceptibility, and the risk of incident dementia: A prospective cohort study.","authors":"Boyue Zhao, Bolun Cheng, Xinyang Li, Jinyu Xia, Yifan Gou, Meijuan Kang, Jingni Hui, Ye Liu, Ruixue Zhou, Chen Liu, Bingyi Wang, Panxing Shi, Feng Zhang","doi":"10.1016/j.tjpad.2025.100078","DOIUrl":"10.1016/j.tjpad.2025.100078","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have revealed how single foods or nutrients affect dementia, but the evidence for a potential link between dietary diversity and dementia is inconsistent.</p><p><strong>Objectives: </strong>This study aimed to evaluate the association between dietary diversity and the risk of incident dementia.</p><p><strong>Design, setting and participants: </strong>This prospective study included 104,572 white participants without dementia at baseline recruited between 2006 and 2010 from the UK Biobank.</p><p><strong>Measurements: </strong>Dietary Diversity Score (DDS) was acquired through the Oxford WebQ's 24-hour dietary recall survey spanning from 2009 to 2012. Cox proportional hazards models were used to estimate the associations between DDS, diversity scores of food groups and the risk of incident dementia. Stratified analyses were subsequently conducted to assess the potential variations across different demographic, socioeconomic, and genetic risk groups.</p><p><strong>Results: </strong>Over a median follow-up period of 10.44 years, 725 participants developed incident dementia. A higher DDS was associated with a lower risk of incident dementia (HR: 0.95; 95 % CI: 0.93-0.97). Stratified analyses revealed statistical significance in this association for individuals under 65 years old (HR: 0.95; 95 % CI: 0.92-0.98), and those with higher polygenic risk scores (PRS; HR: 0.92; 95 % CI: 0.89-0.95). Among five food groups, a higher diversity score for meat and protein alternatives was associated with a lower risk of dementia (HR: 0.92; 95 % CI: 0.86-0.99).</p><p><strong>Conclusion: </strong>Enhancing dietary diversity reduces dementia risk, and is potentially influenced by genetic predisposition. Consuming a diverse range of foods may be an effective strategy against dementia.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100078"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biofluid biomarker changes following treatment with sabirnetug (ACU193) in INTERCEPT-AD, a phase 1 trial in early Alzheimer's disease.","authors":"Erika N Cline, Daniel Antwi-Berko, Karen Sundell, Elizabeth Johnson, Maddelyn Hyland, Hao Zhang, Hugo Vanderstichele, June Kaplow, Robert A Dean, Erik Stoops, Eugeen Vanmechelen, Marleen J A Koel-Simmelink, Charlotte E Teunissen, Gopalan Sethuraman, Todd Feaster, Eric Siemers, Jasna Jerecic","doi":"10.1016/j.tjpad.2025.100082","DOIUrl":"10.1016/j.tjpad.2025.100082","url":null,"abstract":"<p><strong>Objective: </strong>Sabirnetug (ACU193) is a humanized monoclonal antibody selective for soluble amyloid beta oligomers (AβOs), synaptotoxins that are early and persistent triggers of Alzheimer's disease (AD). Sabirnetug pharmacodynamics were examined in the INTERCEPT-AD phase 1 study in mild cognitive impairment and mild dementia due to AD (NCT04931459) using biofluid biomarkers associated with Aβ and tau pathology, synaptic dysfunction, neuroinflammation, and neurodegeneration.</p><p><strong>Methods: </strong>INTERCEPT-AD was a randomized, first-in-human study of sabirnetug versus placebo administered as a single (SAD; 2, 10, 25, 60 mg/kg) or multiple (MAD; three doses of 10 or 60 mg/kg every 4 weeks [Q4W] or 25 mg/kg Q2W) ascending doses. Biomarkers were measured pre-/post-dose in CSF and EDTA-plasma. Correlations of biomarker changes versus dose, exposure duration, and target engagement were determined.</p><p><strong>Results: </strong>In MAD cohorts, CSF pTau181 decreased significantly (60 mg/kg Q4W, p = 0.049). VAMP2 decreased significantly at all doses (p ≤ 0.041); neurogranin decreased significantly at 60 mg/kg Q4W (p = 0.037). Aβ_1-42/Aβ_1-40 trended upward with sabirnetug dose. Aβ_1-42/Aβ_1-40 and neurogranin changes correlated with sabirnetug-AβO target engagement (p ≤ 0.01). Decreases in tTau, VAMP2, and neurogranin correlated with exposure duration (p ≤ 0.007). Plasma pTau181, pTau217, GFAP, and NfL trended lower.</p><p><strong>Discussion: </strong>Following three sabirnetug doses, changes in CSF and plasma biomarkers were observed. The CSF biomarker response increased with increasing dose and exposure duration, consistent with previous reports that sabirnetug reaches the central compartment and engages its AβO target. The ongoing phase 2 ALTITUDE-AD study (NCT06335173) will test whether sabirnetug's pharmacodynamic effects can be substantiated with a larger sample size and longer treatment duration.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100082"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility of computerized motor, cognitive and speech tests in the home: Analysis of TAS Test in 2,300 older adults.","authors":"Guan Huang, Renjie Li, Eddy Roccati, Katherine Lawler, Aidan Bindoff, Anna King, James Vickers, Quan Bai, Jane Alty","doi":"10.1016/j.tjpad.2025.100081","DOIUrl":"10.1016/j.tjpad.2025.100081","url":null,"abstract":"<p><strong>Background: </strong>Early detection of Alzheimer's disease (AD) risk is crucial for dementia prevention. Tasmanian Test (TAS Test) is a novel, unsupervised, computerized assessment of motor, cognitive, and speech function designed to detect AD risk.</p><p><strong>Objectives: </strong>To evaluate the feasibility, usability, and acceptability of TAS Test.</p><p><strong>Design and setting: </strong>TAS Test was administered remotely at home and/or in a research facility, using personal computers.</p><p><strong>Participants: </strong>2,351 adults aged 50-89 years (mean 65.35), 71.76 % female, from Tasmania, Australia.</p><p><strong>Measurements: </strong>Completion rates, ease-of-use, distraction, test duration, and enjoyment scores. Demographics, computer literacy, cognition, and mood were analyzed.</p><p><strong>Results: </strong>Over 80 % completed motor and cognitive components with 92.8 % completing speech tests. 89.81 % found the duration acceptable. 80.90 % of remote and 83.46 % of onsite participants enjoyed the procedure. High usability and acceptability were reported, with age, gender, education, computer literacy, cognition and mood having minimal or no impact.</p><p><strong>Conclusions: </strong>TAS Test demonstrated high completion rates and user satisfaction across a large community sample, supporting its feasibility as an unsupervised computerized assessment tool. Future research should address demographic representation and technical refinements.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100081"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cutting through the noise: A narrative review of Alzheimer's disease plasma biomarkers for routine clinical use.","authors":"M Schöll, A Vrillon, T Ikeuchi, F C Quevenco, L Iaccarino, S Z Vasileva-Metodiev, S C Burnham, J Hendrix, S Epelbaum, H Zetterberg, S Palmqvist","doi":"10.1016/j.tjpad.2024.100056","DOIUrl":"10.1016/j.tjpad.2024.100056","url":null,"abstract":"<p><p>As novel, anti-amyloid therapies have become more widely available, access to timely and accurate diagnosis has become integral to ensuring optimal treatment of patients with early-stage Alzheimer's disease (AD). Plasma biomarkers are a promising tool for identifying AD pathology; however, several technical and clinical factors need to be considered prior to their implementation in routine clinical use. Given the rapid pace of advancements in the field and the wide array of available biomarkers and tests, this review aims to summarize these considerations, evaluate available platforms, and discuss the steps needed to bring plasma biomarker testing to the clinic. We focus on plasma phosphorylated(p)-tau, specifically plasma p-tau217, as a robust candidate across both primary and secondary care settings. Despite the high performance and robustness demonstrated in research, plasma p-tau217, like all plasma biomarkers, can be affected by analytical and pre-analytical variability as well as patient comorbidities, sex, ethnicity, and race. This review also discusses the advantages of the two-point cut-off approach to mitigating these factors, and the challenges raised by the resulting intermediate range measurements, where clinical guidance is still unclear. Further validation of plasma p-tau217 in heterogeneous, real-world cohorts will help to increase confidence in testing and support establishing a standardized approach. Plasma biomarkers are poised to become a more affordable and less invasive alternative to PET and CSF testing. However, understanding the factors that impact plasma biomarker measurement and interpretation is critical prior to their implementation in routine clinical use.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100056"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eligibility for donanemab trial in a population-based study of cognitive aging.","authors":"Katherine E Jones, Jeremiah A Aakre, Anna M Castillo, Vijay K Ramanan, Walter K Kremers, Clifford R Jack, Prashanthi Vemuri, Christopher G Schwarz, Val J Lowe, David S Knopman, Ronald C Petersen, Jonathan Graff-Radford, Maria Vassilaki","doi":"10.1016/j.tjpad.2025.100088","DOIUrl":"10.1016/j.tjpad.2025.100088","url":null,"abstract":"<p><p>The study aimed to assess eligibility for donanemab phase 3 trial in participants of the Mayo Clinic Study of Aging with mild cognitive impairment (MCI) or mild dementia consistent with Alzheimer's disease (AD) clinical syndrome, positive brain amyloid burden, and available tau PET. There were 817 study participants, 60-85 years old, with MCI or dementia consistent with AD clinical syndrome. Applying the Mini-Mental State Examination criteria (20 to 28) and excluding participants with imaging contraindications reduced the sample to 769; 275 participants had amyloid PET available, of whom 130 had also tau PET at the same visit; 56 participants were amyloid positive, had tau PET available at the same visit, and of those, 27 had evidence of tau pathology measured by 18F-flortaucipir PET imaging. Additional eligibility criteria reduced the eligible participants to 23 % (13 out of 56 participants). Neuroimaging findings, central nervous system exclusions, and history of malignancy were the major exclusions.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100088"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fingolimod ameliorates amyloid deposition and neurodegeneration in APP/PS1 mouse model of Alzheimer's disease.","authors":"Meng-Ting Wang, Zi-Cheng Hu, Yang Xiang, Xiao-Qin Zeng, Zhang-Cheng Fei, Jia Chen, Xin-Peng Li, Yu-Peng Zhu, Jun Wang, Yan-Jiang Wang, Zhi-Qiang Xu, Yu-Hui Liu","doi":"10.1016/j.tjpad.2025.100131","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100131","url":null,"abstract":"<p><strong>Introduction: </strong>The immune system plays a critical role in regulating amyloid-beta (Aβ) metabolism in Alzheimer's Disease (AD). Both T and B lymphocytes are involved in the pathogenesis of AD. The sphingosine-1-phosphate (S1P) receptor modulator fingolimod used in the treatment of multiple sclerosis, can promote lymphocyte homing, potentially reducing the infiltration of peripheral lymphocytes into the brain.</p><p><strong>Methods: </strong>In this study, 8-month-old APP/PS1 mice were orally administered fingolimod at a dose of 1 mg/kg/day or saline as a control for 2 months. After treatment, the mice were subjected to behavioral tests, pathological examinations, and biochemical analyses to evaluate behavioral deficits and AD-type pathologies.</p><p><strong>Results: </strong>Fingolimod inhibits the infiltration of peripheral lymphocytes into the brain and reduces neuroinflammation. Fingolimod enhances cognitive function and alleviates brain Aβ deposition. Additionally, fingolimod treatment mitigates other AD-related pathologies, including Tau hyperphosphorylation, neuroinflammation, and neurodegeneration. Proteomic analysis further confirms the therapeutic effects of fingolimod in AD, reflected by the downregulation of proteins involved in multiple AD-associated pathways.</p><p><strong>Discussion: </strong>This study illustrates that fingolimod effectively ameliorates multiple pathological features of AD, highlighting its potential as a promising therapeutic candidate for the disease.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100131"},"PeriodicalIF":4.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}